Dr. Robert Choi is currently a Senior Fellow in the University of Washington's (UW) Division of Allergy and Infectious Disease. He has extensive international experience, including one year with Medicines Sans Frontieres in Darfur as a Medical Team Leader, and recently completed an MPH degree in epidemiology. Dr. Choi's primary goal is to build a career in global HIV/AIDS research. Through the IRSDA he will develop into an independent clinical investigator with expertise in molecular epidemiology and HIV mucosal immunity. His secondary goal is to teach and train future Kenyan investigators and in this way strengthen the collaborative research environment in Nairobi. Dr. Choi is committed to an academic career based in a developing nation, and plans to spend approximately 80% of his time in this setting. Although heterosexual contact is the primary mode of HIV transmission, the transmission rate per contact is low, suggesting that immune factors may mediate transmission risk. This proposal will be nested in an ongoing NIH-funded HIV-discordant couples study and will investigate the role of HIV-1 neutralizing mucosal IgA and IgG on genital shedding of HIV-1 (Aim 1) and HIV-1 transmission to uninfected partners (Aim 2). The final aim will determine the correlates of IgA and IgG responses in HIV-1-infected individuals, including sexually transmitted diseases, bacterial vaginosis, innate factors, and CD4 count (Aim 3). During the award period, Dr. Choi will take formal didactic courses at the UW in epidemiology, biostatistics and immunology and have clinical activities at the Hope Center HIV Clinic in Nairobi one half-day per week. Dr. Carey Farquhar (Primary Mentor) and James Kiarie (On-site Mentor) are experts in conducting HIV-1 prevention research in Kenya and will oversee Dr. Choi's research project and career development. Theii- expertise in epidemiology and clinical HIV research methods will be complemented by input from Dr. Choi's Scientific Advisory Committee, comprised of Dr. Kristina Broliden, basic scientist, and Dr. Barbra Richardson, biostatistician. These 4 individuals will formally evaluate Dr. Choi's progress twice annually based on pre- determined milestones. PUBLIC HEALTH RELEVANCE: This proposal will help us understand the complex interaction between humoral mucosal immunity, HIV-1 shedding in mucosal compartments, and altered HIV infectivity. Understanding this may contribute to development of novel HIV prevention strategies targeting both HIV-uninfected and HIV-infected individuals, such as vaccines and microbicides. Be referenced at this time; include a statement that one from the Registry will be used. Training in the Responsible Conduct of Research: